Altered interaction between triiodothyronine and its nuclear receptors in absence of Cortisol: a proposed mechanism for increased thyrotropin secretion in corticosteroid deficiency states

Abstract

Thyroid hormones occasionally appear less effective when administered alone to patients with panhypopituitarism, and manifestations suggestive of hypothyroidism have been reported in patients suffering from untreated Addison's disease. In the latter condition, thyrotropin secretion is increased: this occurs already after as little as 2 days of temporary withdrawal of therapy with substitution doses of corticosteroids while circulating levels of thyroid hormones remain within normal limits. Therefore, a possible role of cortisol in interaction between triiodothyronine and its nuclear receptors was examined at the level of circulating lymphocytes obtained from patients with primary or secondary adrenocortical failure. The affinity of these receptors was found to be decreased, by more than 50% on average, in the absence of cortisol treatments. This change was promptly corrected upon resumption of therapy. The number of binding sites was not significantly modified. The influence of cortisol on thyroid hormone receptors discussed here might account for the clinical observations mentioned above.

A Case of Cushing Syndrome with Both Secondary Hypothyroidism and Hypercalcemia Due to Postoperative Adrenal Insufficiency

“…In contrast, TSH secretion is enhanced in the presence of glucocorticoid deficiency resulting from adrenalectomy [15] or primary adrenocortical insufficiency [16,17]. In this case, both TSH and FT4 levels were low and levothyroxine replacement was required to maintain thyroid function before the operation.…”

Dexamethasone inhibits the release of TSH from the rat anterior pituitary gland in vitro by mechanisms dependent on de novo protein synthesis and lipocortin 1

“…Thus, the elevations in serum corticosterone/cortisol evident in stress (Zaloga et al 1985), Cushing's syndrome (Benker et al 1990, Rubello et al 1992) and depression (Maes et al 1990(Maes et al , 1994 are accompanied by reciprocal decreases in serum TSH con¬ centration, as are those in ageing subjects (Iovino et al 1991). Conversely, TSH secretion is enhanced in conditions of glucocorticoid deficiency resulting from adrenalectomy (Mitsuma & Nogimori 1982), primary adrenocortical insufficiency (Delayer et al 1987, Ismail et al 1989 or metyrapone treatment (Wilbur & Utiger 1969, Re et al 1976 Kuzuya et al 1990, Iovino et al 1991, Nicoloff ¿5c Spencer 1992 and to actions on the central nervous system (Wilbur & Utiger 1969, Brown & Hedge 1974), notably at the hypothalamic level where dimin¬ ished expression of proTRH mRNA has been reported (Kakucska & Lochan 1991). Little is known of the molecular mechanisms underlying the prompt inhibitory actions of the glucocorticoids at the pituitary level.…”

Physiological Mechanisms in the Adaptive Response of Metabolic Rates to Energy Restriction

“…For instance, basal levels of cortisol and G H contribute to the gluconeogenic response initiated by the decline in plasma insulin levels and the rise in plasma glucagon levels that occur during a short-term fast. Glucocorticoids are also now known to modulate the sensitivity of tissues to T, by increasing the affinity of the nuclear receptors to the hormone (De Nayer et al 1987).…”